Alzheimer's Disease + Antioxidants + Supplements

Supplement May Aid Vascular Dementia Memory ProblemsThe dietary supplement citicoline, which is sold over the counter in 70 different countries, including the United States, appears to help memory in patients with vascular mild cognitive impairment (VaMCI) and may hinder cognitive deterioration, new research suggests. Preliminary results from a longitudinal study presented here at the Alzheimer's Association International Conference (AAIC) 2012 showed that at 9 months, there was a significant difference in Mini–Mental State Examination (MMSE) scores in citicoline users vs nonusers. "If we compare the citicoline group with the nontreatment group, there was a statistically significant difference [in MMSE scores]. On the other hand, we also saw a small increase in activities of daily living [ADL], but this was not statistically significant," principal investigator Pietro Gareri, MD, PhD, Ambulatory Center for Dementia, Catanzaro, Italy, told Medscape Medical News.

The investigators note that vascular disease can impair cognition by reducing cerebral perfusion, causing oxidative stress and neurodegeneration. Research has also shown that vascular dementia, which is the second most common form of dementia, can accelerate atrophy, resulting in white matter abnormalities, asymptomatic infarct, inflammation, and reduced glucose metabolism, cerebral blood flow, and vascular density. Such brain changes, said Dr. Gareri, can have a significant impact on ADL.Acetylcholine Precursor A psychostimulant, citicoline has been shown to inhibit brain cell death associated with cerebral ischemia. It has also been shown to inhibit neurodegeneration and is able to increase neuroplasticity and noradrenaline and dopamine levels in the central nervous system. Furthermore, said Dr. Gareri, it serves as a choline source in the metabolic pathways for the biosynthesis of acetylcholine. In addition, pharmacokinetic studies suggested that it is well absorbed and highly bioavailable with oral dosing. To assess the safety and efficacy of citicoline in elderly individuals with VaMCI, the investigators conducted a multicenter study of 349 participants — 265 in the active treatment group and 84 control participants — aged 65 years and older who had an MMSE score of ≥21, or subjective memory complaints with no evidence of deficits on MMSE, or evidence of vascular lesions on neuroradiology. Those in the active treatment group received oral citicoline at a dose of 500 mg twice a day. Study outcomes included improvement in MMSE scores, ADL, and instrumental activities of daily living (IADL) compared with control participants. Mood was measured using the geriatric depression scale (GDS), and behavioral disorders were assessed by use of the Neuropsychiatric Inventory scale. All participants underwent brain imaging by computerized tomography or magnetic resonance imaging. In addition, they underwent assessment of vitamin B12 and folate levels and thyroid function at baseline and at 3, 6, and 9 months.Boost in Mood The researchers found that after 9 months, those in the active treatment group showed a slight but nonsignificant benefit in MMSE scores (22.4 at baseline, 22.9 after 9 months). However, for those in the untreated control group, MMSE scores declined (21.5 at baseline, 19.6 at 9 months), and this difference was statistically significant. The researchers found no difference between the 2 groups in ADL and IADL scores. In addition, no adverse events were recorded. Dr. Gareri noted that with regard to secondary outcomes of mood and behavior, there was a rise in GDS scores in the citicoline group, although this also was not statistically significant. "This study showed that citicoline is effective and well tolerated in mild vascular cognitive impairment," said Dr. Gareri in a statement. "When cognitive testing scores over 9 months remain unchanged in people developing cognitive impairment, we think this may be considered a good outcome." These findings, he added, indicate that citicoline is safe and efficacious. However, he said, further research is needed. Among other potential hypotheses, Dr. Gareri said it would be interesting to examine whether citicoline could delay the time to treatment with a prescription medication.Need for Replication Commenting on the study for Medscape Medical News, Ralph Nixon, MD, PhD, chair of the Alzheimer's Association Medical and Scientific Advisory Council, said the findings are "encouraging," but noted that they are preliminary."A lot more work [is needed] before we can even suggest it can be used for vascular dementia, even though it is available for that purpose," said Dr. Nixon. A lot of agents have been touted as doing something positive and although many are innocuous, some are not. "In reality, we know relatively little about vascular dementia and how to treat it. The long-term consequences of giving even a neutraceutical type of preparation are unclear. If this [research] group is encouraged by the results, we expect to see replication of the findings and further validation before we know whether it is acceptable or even advisable to use it," he said.Dr. Gareri and Dr. Nixon have disclosed no relevant financial relationships. Alzheimer's Association International Conference (AAIC) 2012. Developing Topics Sessions Presentation 04-12-05. Presented July 18, 2012.Source : MedscapeLink to Source

Antioxidants and Alzheimer's DiseaseConsuming an antioxidant-rich beverage may reduce levels of the amino acid homocysteine, and counter the detrimental inflammatory effects associated with Alzheimer’s disease, suggests a new study reported in.

Daily consumption of the antioxidant-rich drink for eight months was associated with a smaller increase in homocysteine levels, compared with the placebo group, and the effects were even more significant in people with moderate Alzeimer’s disease, according to findings published in the Journal of the Neurological Sciences.

“The main finding of this study is that patients that took DRAP show lower increase in homocysteine concentrations (especially patients of the moderate phase Alzheimer’s Disease),” wrote researchers from the Catholic University of San Antonio in Murcia in Spain.

Previously, epidemiological studies have reported that high levels of homocysteine are associated with suspected or confirmed dementia. Indeed, the Framingham study reported that people with homocysteine (tHcy) levels above 14 micromoles per liter of serum had twice the risk of dementia.

“It is not clear, however, if an elevation of tHcy concentration is a ‘risk factor’ with a direct pathophysiological role in the development of the disease or merely a ‘risk marker’ reflecting an underlying process such as oxidative stress, responsible for both the high tHcy concentrations and the development of Alzheimer’s disease,” explained the researchers.

“At present we know that elevations in plasma tHcy temporally precede the development of dementia and that there is a continuous, inverse linear relation between plasma tHcy concentrations and cognitive performance in older persons,” they added.

Study details

The Murcia-based scientists recruited 100 women to participate in the multicenter, randomized, double-blind controlled clinical trial. Fifty-two of the women were considered generally healthy (no Alzheimer’s) and assigned to the control group, while the other 48 were diagnosed with Alzeimer’s disease (24 women with early-onset and 24 with moderate Alzheimer’s).

Women from all three groups were randomly assigned to one of two interventions: One received a placebo drink for eight months, while the other received an antioxidant beverage rich in polyphenols. The antioxidant beverage was formulated using apple and lemon concentrate juice, apple and green tea extracts, and vitamins B and C.

Results showed that consumption of the antioxidant-rich drink “attenuated the tHcy increase in the control group”, which was measured at a level of 11.7 micromoles per liter for the antioxidant beverage, compared with 15.63 micromoles per liter for the placebo group. Furthermore, in people with moderate Alzeimer’s diseases, the active beverage was associated with an average homocysteine level of 10.49 micromoles per liter, compared with 16.58 micromoles per liter for the placebo group.

“If we take the value tHcy 14.0 micromoles per liter as a ‘risk value’ associated with cardiovascular alterations on neurodegenerative diseases, we can state that this concentration was higher in those subjects that took the placebo drink in the control group and in the group of AD in the moderate phase, whereas the subjects of those groups that took the drink rich in polyphenolic antioxidants beverage maintained their homocysteine levels lower than 14.0 micromoles per liter,” stated the researchers.

Previously, high levels of the amino acid, hyperhomocysteinemia, were said to be a marker for heart disease and thought to be a risk factor for atherosclerotic disease, which contributes to heart attacks.

The link was founded on the observation that children with homocystinuria – a rare genetic condition causing extreme elevations in homocysteine levels – have higher rates of cardiovascular disease. Such an observation was therefore generalized to the wider population, with the hypothesis indicating that supplementation with B vitamins may reduce blood homocysteine levels and reduce the risk of heart disease.

The link between homocysteine and cardiovascular events was questioned recently with results of a meta-analysis of eight folic acid trials involving 37,485 participants finding no benefits on the risk of major vascular events, cancer, or deaths, despite reducing homocysteine levels by 25 per cent.

Researchers from the University of Oxford reported their findings in the Archives of Internal Medicine (Vol. 170, pp. 1622-1631).